Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma
| Autor: | Britton, Edward, Rogerson, Connor, Mehta, Shaveta, Li, Yaoyong, Li, Xiaodun, Fitzgerald, Rebecca C., Ang, Yeng S., Sharrocks, Andrew D. |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Cell Binding
Transcriptional Activation Cell Physiology Esophageal Neoplasms Microarrays Gene Expression Adenocarcinoma Research and Analysis Methods Biochemistry Carcinomas Adenocarcinomas Cell Line Tumor Proto-Oncogene Proteins DNA-binding proteins Genetics Medicine and Health Sciences Humans Gene Regulation Small interfering RNAs skin and connective tissue diseases Non-coding RNA Proto-Oncogene Proteins c-ets Chromosome Biology Biology and Life Sciences Proteins Cancers and Neoplasms Cell Biology Chromatin Assembly and Disassembly Chromatin Regulatory Proteins Nucleic acids Gene Expression Regulation Neoplastic Transcription Factor AP-1 Bioassays and Physiological Analysis Oncology Gene Knockdown Techniques RNA Epigenetics sense organs Adenovirus E1A Proteins Research Article Transcription Factors |
| Zdroj: | PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, genes encoding chromatin remodeling enzymes are frequently mutated in OAC. This is consistent with the emerging concept that cancer cells exhibit reprogramming of their chromatin environment which leads to subsequent changes in their transcriptional profile. Here, we have used ATAC-seq to interrogate the chromatin changes that occur in OAC using both cell lines and patient-derived material. We demonstrate that there are substantial changes in the regulatory chromatin environment in the cancer cells and using this data we have uncovered an important role for ETS and AP1 transcription factors in driving the changes in gene expression found in OAC cells. Author summary Oesophageal adenocarcinoma is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Understanding the molecular causes of this type of cancer will enable us develop more effective treatment strategies which will improve survival rates. Here we have investigated how the genes in cancer cells are packaged into chromatin. We then compare this packaging to normal cells and use this information to identify the molecular causes leading to changes in chromatin packaging in cancer cells. We have identified a regulatory factor called AP1 that acts as a molecular switch to alter gene expression and hence cause cells to adopt a cancer fate. Importantly either this regulatory factor or a coregulatory protein from the ETS family is upregulated in the majority of cancer cells. Our study has therefore uncovered an important regulatory pathway that is commonly activated in oesophageal adenocarcinoma cells. |
| Databáze: | OpenAIRE |
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